Allergic rhinitis and allergic asthma are two closely related diseases characterized by an inappropriate reaction of the respiratory system to stimuli. (A. Gillission, G. Hoeffken, U. R. Juergens: A Connection Between Allergic Rhinitis and Allergic Asthma? The “One-Airway-One-Disease”-Hypothesis. Part 2: Clinical Manifestation, Diagnosis and Shared Therapies. Pneumologe 59 (2005), 192-200). (J. Bousquet: Allergic Rhinitis and its Impact on Asthma (ARIA). Clinical & Experimental Allergy Reviews 3 (1), 43-45). Data from immunologic, genetic and epidemiologic studies point to a systemic link between rhinitis and allergic asthma and which can be seen as manifestations of a common atopic syndrome. Often, the initial reaction of afflicted persons is allergic rhinitis with asthma symptoms appearing years later. These allergic diseases can also progress to affect organs other than the nose, throat and lungs including the eyes, skin and gastrointestinal tract. Additional symptoms include conjunctivitis and other eye related symptoms including eye lid swelling as well as skin related reactions such as atopic dermatitis and psoriasis.
In asthma, the airways become blocked or narrowed causing difficulty breathing. Allergic asthma is characterized by symptoms of coughing, wheezing, shortness of breath or rapid breathing, and chest tightness that are triggered by an allergic reaction to inhaled allergens such as dust mite allergen, pet dander, pollen and mold. Symptoms in asthma patients often can be life threatening. The strong bronchoconstriction and the swelling of the airways can reduce the oxygen and CO2 exchange in the lungs to an extent where patients die from suffocation.
Asthma in general is one of the most common chronic diseases worldwide and a serious global health problem in terms of health care costs and reduced quality of life. People of all ages in countries throughout the world are affected by this disorder although children are particularly susceptible. According to the worldwide Global Initiative for Asthma (GINA), as many as 300 million people worldwide suffer from asthma and this is expected to increase by another 100 million by 2025. Allergic asthma is the most common form, affecting over 50% of sufferers.
Rhinitis symptoms include nasal itching, sneezing, nasal congestion, rhinorrhea (runny nose), and postnasal drainage. Patients with rhinitis frequently have coexisting non-nasal symptoms as well including ocular symptoms, such as itching, swelling, increased lacrimation, and redness. In addition, patients may complain of itching of the throat, constant clearing of secretions from the throat, irritation of the throat, and/or cough. Otic symptoms can include decreased hearing, popping, and fullness. When nasal symptoms are severe, they may be accompanied by itching in the ears and/or palate. There may be interference with aeration and drainage of the paranasal sinuses, resulting in headache or facial pressure or pain. In addition, systemic symptoms, including weakness, malaise, fatigue, poor appetite, and cognitive impairment, have been associated with rhinitis. Allergic rhinitis is not life-threatening, as is allergic asthma, but it can have a significant impact on quality of life.
Generally the treatment of asthmatic patients focuses on measurements of asthma symptoms, sleep disturbance, use of rescue medication, limitations of daily activity, lung function as well as patient and physician assessments. The goal of asthma treatment is well-controlled asthma which is generally regarded as including: symptoms occurring twice per week or less, use of a rescue bronchodilator twice a week or less, no nighttime or early morning awakening, no limitations on exercise work or school, normal peak expiratory flow (PEF) or forced expiratory volume (FEV). Complete or total control of asthma symptoms includes: no asthma symptoms and no rescue bronchodilator use as well as no nighttime or early morning awakening and no limitations on exercise, work or school. Well-controlled asthma is generally a realistic target for most but not all patients. Some patients may wish to achieve complete control. However, some may only be able to achieve well-controlled or completely controlled asthma with medications or doses of medications that cause significant adverse effects. There are also certain patients that can only achieve partial control, for example those with steroid-resistant asthma. In treating allergic asthma, the prevention and interference with life threatening bronchioconstriction episodes is a prime goal (W T. Watson, A. B. Becker, F. E. Simpson: Treatment of allergic rhinitis with intranasal corticosteroids in patients with mild asthma: effect on lower airway responsiveness. J Allergy Clin Immunol. 91 (1993), 97-101).
Several treatment options exist for rhinitis and asthma. However, all treatments known to date provide only symptom modification or even only acute symptom reduction without interfering with the cause of the disease or the disease progression. In general, treatments may be life style modification to reduce the exposure to stimuli, anti-inflammatory medication to relieve the inflammation related symptoms, inflammatory mediator release inhibitors to reduce the effect of single mediators such as histamine or individual interleukins, symptomatic relievers such as anticongestants or bronchodilating agents and finally immune globulins to reduce the immune globulin E driven reaction. With the exception of immune globulin E treatment, the options for achieving control of asthma symptoms require the repeated (daily) prophylactic or metaphylactic administration of drugs. The immune globulin E treatment is the one exception in that it may be administered every few months. There are no treatment options that control the appearance of asthma symptoms for a period of 1 or 2 years.
The complicated combination of chronic medications to reduce the frequency and severity of attacks with short acting inhaled drugs to reduce symptoms during an attack makes clear that current treatments are not optimal. Undesirable drug related side effects arise from the use of steroids and beta agonists. The treatment to reduce immune globulin E antibodies is a useful improvement but the intervention must be repeated every few months. As well with the use of antibodies in general, the likelihood is high that the body will identify the administered antibodies as foreign and develops neutralizing antibodies in response. Furthermore, the current treatments focus on the treatment of symptoms but not of the disease or the cause of the disease. Currently there are no treatments available that prevent the allergic reaction from occurring in response to allergen exposure.
There is thus a medical need to have improved treatments for rhinitis, asthma and atopic diseases such as atopic dermatitis. A therapy that reduces the requirement for daily treatments would be a substantial improvement.